Chronic exposure to hypoxia attenuates contractile responses in rat airways in vitro: a possible role for nitric oxide

Clayton, R.A.E.; Nally, Jane E.; MacLean, Margaret R.; Thomson, Neil C.; McGrath, J.C.

doi:10.1016/s0014-2999(99)00693-7

Cited by 10 publications

(19 citation statements)

References 23 publications

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“…By contrast, CH markedly decreased the maximal contractile response normalized to SMA. This finding is in agreement with that of Clayton et al (6) obtained in similar hypoxic conditions in young rats (28-to 30-days old). The fact that CH enhances calcium signaling and decreases airway reactivity strongly indicates that it decreases the calcium sensitivity of the contractile apparatus.…”

Section: Discussionsupporting

confidence: 94%

“…Such a protocol generates CH, which in turn provokes pulmonary artery hypertension and right ventricular hypertrophy, shown by an increase in the ratio of right ventricle-to-left ventricle-plus-septum weight (RV/LVS) (1,6,20,22). We measured, in a subset of the present animal population, the parameter RV/LVS (0.51 Ϯ 0.02, n ϭ 6) and found it increased consistently with previous studies (1,22,30).…”

Section: Chsupporting

confidence: 77%

“…Previous studies that have evaluated the effect of CH on rat tracheal hyperresponsiveness produced conflicting results. Clayton et al (6,7) reported that CH attenuates contractile responses in rat airways in vitro, whereas Belouchi et al (1) indicated that CH increases calcium responses in rat tracheal myocytes. In the present study, we have reexamined the effect of CH on the mechanical activity of rat isolated tracheal muscle with special attention to the normalization of the isometric force, since CH may induce smooth muscle remodeling (10,14).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike the interaction between asthma and air pollution that has largely been investigated by epidemiological, clinical, as well as experimental studies (16,17,29), very little is known about the combined effect of air pollution and chronic hypoxia (CH), a condition that is frequently observed in patients suffering from COPD (21,31). The effect of CH, per se, on airway responsiveness remains unclear, since very few experimental studies have addressed this issue (1,6).…”

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confidence: 99%

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Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity

Roux

Duvert

Marthan

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Roux, Etienne, Michel Duvert, and Roger Marthan. Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity. Am J Physiol Lung Cell Mol Physiol 283: L628-L635, 2002. First published April 19, 2002 10.1152/ajplung.00387.2001.-This study investigated the interaction between exposure to air pollutants and chronic hypoxia (CH). We used a hypobaric chamber (14 days at barometric pressure 380 mmHg) to produce CH in rats. Exposure to various doses of acrolein or ozone did not modify the mechanical response to cholinergic agonists. Exposure to 3 M/min acrolein did not alter epithelium-free trachea responsiveness. In contrast, direct exposure of freshly isolated myocytes to 2 and 3 M/min acrolein enhanced the amplitude of the first intracellular [Ca 2ϩ ] rise in response to 0.1 M ACh and the calcium oscillation frequency in response to 10 M ACh. CH alone did not alter smooth muscle cross-sectional area (SMA) or epithelium-plus-submucosa thickness. CH decreased maximal contractile response (maximal force normalized to SMA) but increased sensitivity (pEC 50) to cholinergic agonists. We conclude that unlike in normoxic rats, exposure to air pollutants does not induce airway hyperresponsiveness in CH rats, although it increased calcium signaling. These results cannot be explained by change in smooth muscle accessibility, but may be linked to the effect of CH on calcium-contraction coupling.ozone; acrolein; smooth muscle; rat trachea; excitation-contraction coupling INHALATION OF AIR POLLUTANTS induces airway hyperresponsiveness and, therefore, poses a possible risk to human health, especially in patients whose airways are already compromised by preexisting pathologies such as asthma or chronic obstructive pulmonary disease (COPD) (8,9,11). Unlike the interaction between asthma and air pollution that has largely been investigated by epidemiological, clinical, as well as experimental studies (16,17,29), very little is known about the combined effect of air pollution and chronic hypoxia (CH), a condition that is frequently observed in patients suffering from COPD (21, 31). The effect of CH, per se, on airway responsiveness remains unclear, since very few experimental studies have addressed this issue (1, 6).We previously reported that ex vivo administration of a variety of gas pollutants, such as ozone or acrolein, to either human lung or rat isolated airways alters the subsequent in vitro mechanical response (2-4, 26, 29). This alteration is related to changes in calcium signaling at the site of the smooth muscle cell (15, 28). We have also developed an experimental model of CH using a hypobaric chamber and observed that CH modifies the mechanical response of isolated airways as a consequence of an effect on calcium signaling (1, 5).The aim of the present study was thus to investigate the interaction between CH and exposure to pollutants in rat isolated trachea. We examined the effect in CH rats of preexposure to ozone and acrolein on the contractile response to muscarinic stimulation i...

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Section: Discussionsupporting

confidence: 94%

Section: Chsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity

Roux

Duvert

Marthan

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In vitro, O 2 levels are suggested to modulate ASM cell growth, with moderate hypoxia inducing and severe hypoxia inhibiting cell proliferation (10). At the tissue level, chronic hypoxia results in hyperplasia of bronchial smooth muscle (26), increased sensitivity of ASM to cholinergic agonists (3), and epithelium-dependent attenuation of contractile responses in isolated rat trachea, which is reversed on removal of the epithelium (9). Therefore, an interplay appears to exist between the hypoxia response pathway and physiological functions of ASM cells, including their contractile properties.…”

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confidence: 99%

Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1α and airway responsiveness to ACh

Chachami

Hatziefthimiou²,

Liakos³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chachami G, Hatziefthimiou A, Liakos P, Ioannou MG, Koukoulis GK, Bonanou S, Molyvdas P-A, Simos G, Paraskeva E. Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1␣ and airway responsiveness to ACh. Am J Physiol Lung Cell Mol Physiol 293: L913-L922, 2007. First published July 27, 2007; doi:10.1152/ajplung.00459.2006.-Airway smooth muscle (ASM) cells are characterized by phenotypic plasticity and can switch between differentiated and proliferative phenotypes. In rabbit tracheal ASM cells that had been differentiated in vitro by serum starvation, readdition of FBS caused initiation of proliferation and induction of nuclear and transcriptionally active hypoxia-inducible factor (HIF)-1␣. In addition, FBS stimulated the induction of HIF-1␣ by the hypoxia mimetic cobalt. Treatment with actinomycin D, cycloheximide, the phosphatidylinositol 3-kinase inhibitors LY-294002 and wortmannin or the reactive oxygen species scavenger diphenyleneiodonium inhibited the FBS-dependent induction of HIF-1␣. These data indicate that, in differentiated ASM cells, FBS upregulates HIF-1␣ by a transcription-, translation-, phosphatidylinositol 3-kinase-, and reactive oxygen species-dependent mechanism. Interestingly, addition of FBS and cobalt also induced HIF-1␣ in organ cultures of rabbit trachea strips and synergistically increased their contractile response to ACh, suggesting that HIF-1␣ might be implicated in airway hypercontractility. cobalt; fetal bovine serum AIRWAY SMOOTH MUSCLE (ASM) cells of trachea and bronchi are important for O 2 homeostasis, since they control the diameter of the airways and regulate the amount of air that reaches the lungs. Smooth muscle cells are not terminally differentiated but retain phenotypic plasticity and switch between contractiledifferentiated and synthetic-proliferative phenotypes with unique morphological, biochemical, functional, and gene expression characteristics (21). Inflammation and injury promote acquisition of the proliferative phenotype and cause hyperplasia and hypertrophy of ASM, which in turn result in airway narrowing (24). These phenotypic changes can be reconstituted in vitro in ASM cell cultures, which have been used to study airway remodeling (19,20). ASM cell proliferation is mainly controlled by the phosphatidylinositol 3-kinase (PI3K) and MAPK pathways (1, 51), which are activated by growth factors present in serum.In ASM, as in most other cell types, cellular proliferation is closely linked to the availability of O 2 . In vitro, O 2 levels are suggested to modulate ASM cell growth, with moderate hypoxia inducing and severe hypoxia inhibiting cell proliferation (10). At the tissue level, chronic hypoxia results in hyperplasia of bronchial smooth muscle (26), increased sensitivity of ASM to cholinergic agonists (3), and epithelium-dependent attenuation of contractile responses in isolated rat trachea, which is reversed on removal of the epithelium (9). Therefore, an interplay appears to exist between the hyp...

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Ischemic and Peroxynitrite Preconditioning Effects in Chronic Hypoxic Rat Lung

Turan

Yıldız

Gümüşel

et al. 2008

Experimental Lung Research

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Chronic hypoxic pulmonary hypertension is characterized by vasoconstriction and vascular remodeling and impaired endothelial nitric oxide (NO) production. Although ischemic preconditioning of the lung leads to protective effect against ischemic reperfusion injury, the mechanisms of this protection are not well documented in the lung. The aim of this study was to investigate the effects of chronic hypoxia on preconditioning induced by ischemia or peroxynitrite in isolated rat lungs. The isolated rat lung, from exposed to hypobaric hypoxia for 21 days, was mounted on a modified Langendorff perfusion apparatus. Lungs were preconditioned by either 5 minutes' ischemia and 5 minutes' reperfusion or 10 microM peroxynitrite prior to 2 hours of normothermic ischemia. Although ischemia-reperfusion or peroxynitrite preconditioning markedly reduced KCl responses on perfusion pressure, phenylephrine-induced responses were not significantly modified. Pretreatment of the hypoxic lungs with peroxynitrite scavenger, uric acid, or poly (ADP-ribose) synthase inhibitors (PARS), 3-aminobenzamide (3-AB) or nicotinamide, did not modify the KCl- and phenylephrine-induced responses in chronic hypoxic lungs. There were also no marked differences either in wet to dry weight ratio or malondialdehyde levels of chronic hypoxic lungs. These results imply that preconditioning does not occur in the chronic hypoxic rat lungs.

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Chronic exposure to hypoxia attenuates contractile responses in rat airways in vitro: a possible role for nitric oxide

Cited by 10 publications

References 23 publications

Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity

Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity

Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1α and airway responsiveness to ACh

Ischemic and Peroxynitrite Preconditioning Effects in Chronic Hypoxic Rat Lung

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